Antidementia Drugs Contribute to Longer Life

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Survival (life span) in people with Alzheimer's is recognized to be shorter than what is expected in cognitively normal seniors and is recognized to be influenced by several factors including age, disease severity, general debility, and gender. Approved antidementia drugs have been shown help with the symptoms of Alzheimer's but their influence on life span is not known.
At ICAD 2008, Susan Rountree, MD, of the Alzheimer's Disease and Memory Disorders Center of Baylor College of Medicine in Houston, Texas, reported on a study of the persistent use of antidementia drugs and their influence on survival.
The researchers followed 641 people diagnosed with Alzheimer's at an academic medical clinic between 1989 and 2005. These individuals had been on drug therapy over the course of their Alzheimer's for variable amounts of time and the majority had used one or more of the commercially available antidementia drugs (donepezil, galantamine, rivastigmine, tacrine, or memantine).
Total years on medication was divided by the total years of disease symptoms to determine a persistency score for each individual. Participants were divided into four groups (1st, 2nd, 3rd, 4th quartiles) ranging from the lowest to highest persistency scores and the researchers compared life span among the groups after adjustment for a variety of factors generally recognized to influence survival. The 1st quartile took drug less than 33 percent of the time, 2nd quartile = 34-55 percent of the time, 3rd quartile = 56-70 percent of the time, and the 4th quartile = 71-99 percent of the time.
Over the entire course of the study, 12 percent of participants never took any antidementia drugs. Fifty-three (53) percent of the participants died.
The researchers found an inverse and statistically significant relationship between the overall risk of death and the persistency of drug use. Those in the lowest persistency group (1st quartile) were 2.4 times more likely to die than those in the highest persistency group (4th quartile). Those with intermediate drug exposure had increased risk of death of 2.2 times (2nd quartile) and 1.5 times (3rd quartile) compared to the most persistent users. More persistent therapy was associated with a longer median survival time; the median survival between the lowest quartile group and the most persistent users was 3.12 years.
"In our study, people with Alzheimer's who took antidementia drugs more persistently lived longer than those who took the medications for shorter time intervals," Rountree said. "In an earlier study involving this group, we reported that persistency of treatment was also associated with long term cognitive and functional benefits. Persistent drug therapy appears to help Alzheimer's patients live longer and the mechanism may be related to overall improvement of cognition and function resulting from current symptomatic therapies." ...http://www.medicalnewstoday.com

Med diet in decline on home turf

Populations around the Mediterranean are abandoning their traditional healthy diets, the FAO warns, as incomes increase and consumers opt for more meat, saturated fats and time-saving processed foods. ...http://www.nutraingredients.com

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Risk Factors for Progression to Dementia

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In the general population, many risk factors and predictors for dementia have been identified. However, a combination of risk factors may give a more accurate prediction for dementia than each individual risk factor.
Sylvaine Artero, of INSERM, Montpellier, France; Pieter Jelle Visser, of the University of Maastricht, The Netherlands; and colleagues analyzed a pooled database constructed from nine European surveys of dementia risk factors, including a total of 16,261 participants over age 55 without dementia. Potential risk factors were evaluated at baseline and incident dementia was assessed over a follow up period of up to 15 years. Risk factors included cardiovascular disorders, endocrine disorders, depression, head trauma, intoxicants (including alcohol, smoking and drugs), physical and intellectual activities, performance in activities of daily living, Apolipoprotein E genotype, cognitive complaint, and cognitive test performance.
In total, 1,530 subjects (9%) progressed towards dementia. In order, the most predictive variables were: impairment in executive function (planning), memory problems (as measured on tests), subjective complaints about memory/cognitive failure, Apolipoprotein E (ApoE) genotype, use of psychotropic medication, severe head trauma, diabetes, stroke, and problems with language. In addition, problems with activities of daily living, smoking, no drinking, no use of hypertensive drugs, low education, and female gender all independently predicted dementia at follow-up.
"Cases of dementia in the general population can be best identified by a combination of socio-demographic, clinical and cognitive factors," said Artero. "Developing a better understanding of the factors that increase risk for Alzheimer's will help us to create more effective methods to prevent people from developing the disease." ...http://www.medicalnewstoday.com

Soft drink formulation: hard work ahead

As soft drink makers face growing criticisms over the potential detrimental health impacts of some of their ingredients, BeverageDaily.com takes a look at how the industry is adapting to ever-changing market concerns in the first of a two part article. ...http://www.nutraingredients.com

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Risk assessment and early detection of Alzheimer's

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Researchers have previously found elevated β-secretase (BACE1) activity in the brains of patients with Alzheimer's compared to healthy individuals. BACE1 is one of two enzymes involved in the pathological processing of amyloid precursor protein (APP) and the production of toxic Aβ (beta amyloid, the main constituent of amyloid plaques in the brains of people with Alzheimer's).
Professor Harald Hampel, of Trinity College Dublin, Ireland and the University of Munich, Germany, Professor Yong Shen, of Sun Health Research Institute, USA, and colleagues investigated whether BACE1 assessed in cerebrospinal fluid (CSF) may be a feasible biomarker candidate for predicting Alzheimer's in people with mild cognitive impairment (MCI). MCI is a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer's.
The research had two parts. In the first part, the scientists measured BACE1 levels in CSF in 80 people with Alzheimer's, 59 people with MCI, and 69 healthy elderly controls (HC) at two independent, international research centers. MCI subjects showed highly increased levels of BACE1 activity when compared to HC and people with Alzheimer's. BACE1 activity was significantly correlated with Aβ level. A subsequent validation study replicated these initial findings in a new and independent set of 41 people with Alzheimer's, 46 with amnestic MCI and elderly HC.
In the second part, 47 MCI subjects were clinically followed up over two years to assess the predictive value of BACE1 in combination with other biomarker candidates for predicting the conversion from MCI to Alzheimer's. The additional candidates were abnormal brain proteins total tau and phosphorylated tau measured in CSF, and baseline performance on a large neuropsychological testing battery. Fifteen (15) MCI subjects converted to Alzheimer's after a mean follow-up interval of 2.3 years. Analysis showed that BACE1 protein levels and ApoE genotype (a genetic risk factor for Alzheimer's) were the strongest predictors of conversion to Alzheimer's, after controlling for age and gender. The classification accuracy was 78%, the sensitivity was 80%, and the specificity was 77% for the combined model.
"These important findings pave the way for further rigorous assessment of BACE1 as an effective and accurate clinical diagnostic tool, which could significantly improve risk assessment and early detection of Alzheimer's," Hampel said. "We believe that BACE1 will be an excellent outcome biomarker to look at in ongoing clinical trials of anti-amyloid, disease modifying therapies. Furthermore, we are working on a blood-based diagnostic test for BACE1 as well."...http://www.medicalnewstoday.com

Omega-3s more effective for mental slowdown than Alzheimer’s: study

Brain benefits from regular intake of omega-3 fatty acids may be more pronounced in people with mild cognitive decline than people with mild Alzheimer’s: study. ...http://www.nutraingredients.com

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Daily communication between people with Alzheimer's

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Over their years together, family members often develop assumptions and expectations about their conversational roles and responsibilities. With the onset and progression of Alzheimer's, the person with dementia becomes less able to speak as others have always expected him or her to. Impaired word finding is often the first, most noted difficulty. Shortened attention span and/or impaired recent memory results in the individual no longer being able to follow another speaker's retelling of the day's events. In an attempt to participate in the conversation, the person with dementia may say something that shows confusion or misunderstanding. He may initiate an unrelated topic because he cannot remember what had just been discussed. These responses are not normally anticipated and may leave caregivers in a momentary quandary as to how to continue conversations.
Jeanne Katzman, CPhil, CCC/SLP of the University of California Los Angeles, examined the effects of Alzheimer's on family conversation at dinnertime. Thirty (30) families in which one member had recent onset of Alzheimer's participated in the three-year study, which began in 2001. Each family had two videotaped dinner conversations which were later transcribed and analyzed for both verbal and gestural communication. The goal was to document ordinary family communication based on naturally occurring conversation and to analyze problematic sequences.
According to Katzman, responses of healthy family members to utterances of the Alzheimer's individual were found to follow certain predictable patterns. When a response was unexpected and disrupted the normal flow of conversation, healthy family members often were observed to continue their talk almost if the person with Alzheimer's had not spoken. The healthy family members tended to pause – a sign that the utterance was indeed heard – but did not respond verbally. In such sequences, the healthy speaker's lack of response framed the Alzheimer's individual as a non-participant.
Katzman found that other families responded to each problematic utterance. In extended, multigenerational families (n=7), a healthy family member might respond with an explanation of the utterance and then speak for the person with Alzheimer's. Conversations between families with only two members (n=21) organized problematic talk in a greater variety of ways. Responses often took the form of rewording; the healthy speaker suggested what the other wanted to say, expanded upon it, and brought the contribution of the family member with Alzheimer's to a close.
"This initial research leads to an improved understanding of daily communication between people with Alzheimer's and their families. This will be used to develop new training programs that focus on facilitating conversation between family members," said Katzman. "The goals are for caregivers to have the opportunity to adjust their conversation with the changing communicative and cognitive abilities of their loved ones and for people with Alzheimer's to experience healthier participation in family discussions." ...http://www.medicalnewstoday.com

Europe approves new vegetarian omega-3 source

UK-based supplier Croda Health Care has won European Union Novel... http://www.nutraingredients.com

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Maintaining cardiorespiratory fitness modify Alzheimer’s

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Exercise and physical fitness have been shown to moderate age-related regional brain volume changes in healthy older adults. However, little is known about the relationship of fitness to Alzheimer’s disease-related brain changes, particularly in areas that are predominantly affected early in the course of the disease, such as the hippocampus.
Robyn A. Honea, PhD, and colleagues from the University of Kansas Medical Center, Kansas City, Kansas investigated the relationship between cardiorespiratory fitness and regional brain volume in healthy older adults and those with early Alzheimer’s using MRI and a new neuroimaging analysis technique called voxel-based morphometry.
Nondemented (n=56) and early-stage Alzheimer’s subjects (n=63) aged 60 and over had MRI scans and fitness assessments based on peak oxygen consumption during a treadmill test. The researchers found that people with early Alzheimer’s in the study, and not healthy elderly, had a significant relationship between the size of key brain areas associated with memory (hippocampal and parahippocampal volume) and cardiorespiratory fitness, such that those with better fitness ratings had less atrophy and those with worse fitness ratings had more atrophy.
"We found that, in early-stage Alzheimer’s, cardiorespiratory fitness is correlated with regional brain volumes in key areas affected by the disease," said Honea. "This suggests that maintaining cardiorespiratory fitness may positively modify Alzheimer’s-related brain atrophy."
"A previous study by our group looked at whole brain volumes and fitness, giving us a clue that there was some relationship. This is the first study to get an inside look into specifically where these changes occur in the brain – we're able to locate the changes associated with fitness to the actual memory region, the hippocampus, which is a key area for Alzheimer’s-related atrophy," Honea added. ...http://www.medicalnewstoday.com

Omega-3-rich fish linked to better hearts in Japan

Large intakes of omega-3 fatty acids from fish may explain... ...http://www.nutraingredients.com

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The central role of amyloid-ß in the Alzheimer's risk

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The editors of Neurotherapeutics are pleased and proud to announce their July issue, devoted to "Novel Therapeutics for Alzheimer's Disease." Neurotherapeutics (http://www.neurotherapeutics.org) is the journal of the American Society of Experimental NeuroTherapeutics (ASENT) www.asent.org. The issue coincides with the 2008 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD), being held at McCormick Place, Chicago, July 26 to 31, 2008. Rudolph E. Tanzi, Ph.D., of the Massachusetts General Institute for Neurodegenerative Disease and Massachusetts General Hospital, is a Guest Editor. "In this issue of Neurotherapeutics, we have enlisted several experts in the field to review the most promising new therapeutics currently under development for the treatment and prevention of AD," Dr. Tanzi writes in the introductory editorial.

The eleven papers in the special issue highlight promising therapeutic targets for Alzheimer's disease, providing an update on efforts to develop treatments. Given the central role of amyloid ß peptide (Aß) in the pathogenesis of Alzheimer's disease, cerebral accumulations of Aß are a major focus. The lead article in the issue looks at techniques for measuring the effects of disease-modifying therapies on cerebral Aß levels including the key question of whether they correlate with cognitive performance.

Clinical trials aimed at all of these therapeutic targets are underway. In his editorial, Dr. Tanzi expresses "cautious optimism and high hopes" that these trials may lead to new therapeutic approaches to Alzheimer's disease. He concludes, "With several active clinical trials and other promising drugs now headed toward the clinic, the hope is that we will soon have novel AD therapeutics that successfully slow or reverse disease progress in AD." ...http://www.medicalnewstoday.com

Vitamin C-rich diet may slash diabetes risk

Increased blood levels of vitamin C may reduce the risk... ...http://www.nutraingredients.com

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The membrane model to study of Alzheimer's

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Researchers at the National Institute of Standards and Technology (NIST) and three collaborating institutions are using a new laboratory model of the membrane surrounding neurons in the brain to study how a protein long suspected of a role in early-stage Alzheimer's disease actually impairs a neuron's structure and function. The team's findings are reported in a new paper in the Biophysical Journal.

The brain's neurons transmit nerve impulses down a long stem that is surrounded by a two-layer membrane. In the neuron's normal, "rest" state, this membrane actively sorts sodium ions to the outside of the cell and potassium ions to the inside. To transmit a nerve impulse, an electrochemical change ripples down the membrane in advance of the impulse, making it temporarily more permeable and allowing the ions to swap places. That in turn changes the electrical potential across the membrane, allowing the impulse to pass. Afterwards, the membrane returns to rest and begins sorting the ions again.

Medical experts have hypothesized for years that small polypeptides called amyloid beta peptides somehow create a "leaky" membrane that disrupts this balanced back-and-forth switching of the electrical potential and, in turn, normal impulse transmission. Alzheimer's disease the progressive brain disorder that is the nation's sixth leading cause of death is believed to start with such breakdowns. As the disease progresses, amyloid beta peptides clump together to form plaques that further destroy nerve function.

Studying the beginnings of Alzheimer's is nearly impossible in humans because by the time the disease is diagnosed, most patients have moved into its later stages. Researchers at NIST have developed a laboratory model that recreates a simplified version of the nerve cell membrane, allowing the study of Alzheimer's disease mechanisms at the molecular level. A clever piece of molecular-level design, the system is built by first covering a silica surface with gold. Sulfur atoms, which bond well to gold, are then added to act as anchors to hold the bilayer membrane. The result is a stable, tethered membrane with an aqueous environment on both sides that accurately models the behavior of the nerve cell membrane.

A collaborative team of researchers from NIST, Carnegie Mellon University, the University of California-Irvine and the Biochemistry Institute (BCHI) in Vilnius, Lithuania, exposed the membrane model to different concentrations of a specific form of amyloid beta peptides comprised of soluble, tiny (5-6 nanometers, approximately twice the diameter of a DNA helix) chains. The researchers found increased cation movement across the normally strong barrier at the higher concentrations of the peptides. The data support the hypothesis that membrane "leakiness" is not due to a permanent hole being formed but rather to an aggregation of amyloid beta peptides in the membrane that allows cations to be passed from peptide to peptide across the bilayer, like a baton handed off by relay runners.

The researchers are continuing to use their model system to better understand the role amyloid beta peptides play in early-stage Alzheimer's disease. Future plans include investigating how amyloid beta peptide aggregates arrange themselves in the membrane, how the peptide aggregates affect or influence calcium channels (portals for calcium ion movement) in the membrane, and how the peptides interact with membranes constructed with other types of lipids. ...http://www.medicalnewstoday.com

Microdispersed cellulose shows heart benefits: animal study

A dietary supplement containing microdispersed oxidised cellulose may reduce cholesterol levels by about 20 per cent, according to a new study. ...http://www.nutraingredients.com

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